Abstract Obstructive sleep apnea (OSA) needs to be treated with devices that will be utilized with greater compliance by patients than is currently the case with positive airway pressure. To this end, we recently showed that increased inspired CO2 via rebreathing was effective in reducing most obstructive and central apneas in OSA patients. Then, our UW team of bioengineers, physiologists, and sleep physicians built a novel variable dead space rebreathe device?with no added positive pressure?which monitors breath by breath ventilation and automatically adjusts the rebreathe dead space volume to add or subtract the level of inspired CO2 depending on the degree of sleep disordered breathing. This approach provides the minimum effective CO2 dose needed in individual OSA patients to stabilize central respiratory motor output and to recruit upper airway dilator muscles, thereby treating obstructive and central apneas. We propose to determine the effectiveness of this ?Smart CO2? treatment as well as its effects on sleep state stability, sleep quality, and blood pressure in 15 moderate to severe OSA patients studied over several nights. We expect the findings from the proposed study to be sufficient to determine if the ?Smart CO2? treatment is a viable approach to OSA treatment worthy of testing in a clinical trial.